Incidence and variables associated with short and long-term mortality in patients with systemic lupus erythematosus and sepsis admitted in intensive care units.

Background Infections are common among patients with systemic lupus erythematosus (SLE), and are associated with increased morbidity and mortality. Objectives To determine whether SLE is an independent risk factor for short- and long-term mortality in patients admitted to an intensive care unit (ICU) with sepsis, and to identify the characteristics of SLE patients admitted to an ICU with sepsis. Methods A retrospective age- and sex-matched cohort study, based on data of the SEPSIS-ISR (Sepsis Israel) Registry, an ongoing study that collects data on all patients admitted with sepsis to the ICUs. The primary outcome was to determine whether SLE is an independent risk factor for 30-day and 3-year mortality. Secondary outcomes were 30-day and 3-year survival rates, and the identification of variables associated with mortality within the group of patients with SLE. Results In total, 29 SLE and 87 non-SLE patients (median age 55 years; 79.3% females) were included. The primary sites of infection as well as pathogen distributions were similar between the two groups. The most common infections among the SLE and non-SLE patients were pneumonia (48.3 vs. 31%, p = 0.09), urinary tract infection (20.7 vs. 14.9%, p = 0.56) and peritonitis (13.8 vs. 16.1%, p = 0.77). Severe sepsis and septic shock were diagnosed in 79.3 versus 80.5% ( p = 0.89) and 55.2 versus 33.3% ( p = 0.04) of the SLE and non-SLE patients, respectively. The 30-day and 3-year survival rates did not differ between SLE and non-SLE patients, and were 69 versus 67.8% ( p = 0.79) and 41.4 versus 47.1% ( p = 0.69), respectively. In multivariate Cox regression analysis, age (hazard ratio (HR) = 1.02; 95% confidence interval (CI) 1.00-1.05) and cardiovascular involvement during sepsis (HR = 3.32; 95% CI 1.4-7.86) were significant independent risk factors for 30-day mortality. Multiorgan dysfunction during sepsis admission was associated with increased 3-year mortality (HR = 1.37; 95% CI 1.07-1.75). Conclusions SLE is not an independent risk factor for 30-day or 3-year mortality following ICU admission with sepsis. Increased late mortality was associated with congestive heart failure within the SLE patients alone. None of the SLE-related variables were statistically different between the living and deceased SLE patients.

Safety of vaccination of patients with systemic lupus erythematosus.

Live vaccines are not safe for immuno-compromised patients and should not be given to patients with systemic lupus erythematosus. In addition, all vaccines are not recommended for systemic lupus erythematosus patients when their disease is very active and mainly for patients with very active lupus nephritis. Systemic lupus erythematosus patients with quiescent or mildly active disease should be encouraged to receive vaccination according the recommendations given by the Immunization Practices Advisory Committee. Among this group of systemic lupus erythematosus patients, vaccines are safe and they do not affect the clinical manifestations of systemic lupus erythematosus including renal features, disease activity, or the requirement for steroids or cytotoxic drugs. However, vaccines may trigger the generation of autoantibodies which is usually short term and has no clinical significance. In individual cases vaccines exacerbate systemic lupus erythematosus; however, no specific clinical or laboratory variables have been identified to be associated with flare of systemic lupus erythematosus following vaccination.

Anticardiolipin antibodies in systemic lupus erythematosus: clinical and laboratory correlations.

PURPOSE: To examine the link between anticardiolipin antibodies and the features of antiphospholipid syndrome in patients with systemic lupus erythematosus (SLE). PATIENTS AND METHODS: In this prospective cohort study conducted in a single center, 390 SLE patients were followed up between June 1991 and 1994. At each assessment, a complete history, physical examination, and laboratory evaluation (including measurement of anticardiolipin antibodies) were performed according to a standard protocol. RESULTS: Forty-seven percent of the patients had an elevated level of anticardiolipin antibodies. In the univariate analysis, elevated anticardiolipin antibody levels were found to correlate with thrombocytopenia (P = 0.006), prolonged activated partial thromboplastin time (aPTT) (P = 0.003), and positive direct and indirect Coombs' test result's (P < 0.001). No correlation was identified with any of the clinical features of antiphospholipid syndrome. In the multivariate analysis, anticardiolipin antibodies remained highly associated with thrombocytopenia (odds ratio [OR] 4.05, P = 0.02), positive direct Coombs' test (OR 2.31, P < 0.001), and prolonged aPTT (OR 1.73, P = 0.03). In the multivariate model using venous/arterial thrombosis as the outcome variable, only prolonged aPTT was associated with venous/arterial thrombosis (OR 7.9, P < 0.001). None of the laboratory variables were found to correlate with fetal loss. CONCLUSIONS: The presence of anticardiolipin antibodies in patients with SLE is associated with prolonged aPTT, thrombocytopenia, and positive Coombs' test result, but not with antiphospholipid syndrome. Prolonged aPTT is strongly associated with venous/arterial thrombosis.

Molecular mimicry between host and pathogen: examples from parasites and implication.

The studies summarized in this paper suggest that parasites may trigger activation of autoimmune mechanisms. The association between parasites and autoimmunity could by manifested by the development of pathogenic anti-parasitic antibodies and cytotoxic T cells that attack and damage self tissues as a result of molecular mimicry between host and parasites. On the other hand, the homology between self and parasitic antigens may enable parasites to protect themselves from the immune system and to induce a state of immunosuppression. Although classic autoimmune diseases have not been shown to be more common amongst patients with chronic parasitic infections than in the general population, it is clear that autoimmune activity does occur in patients with chronic parasitic infections. It is possible that infection with parasites and other microbial agents may be followed by the activation of the immune system and, in genetically predisposed individuals, by loss of functional tolerance to self, activation of autoreactive cell that leads to progression to an overt autoimmune disease.

Gastrointestinal manifestations of systemic sclerosis.

Gastrointestinal (GI) manifestations of systemic sclerosis (SSc) were found in 82% of 262 patients followed up prospectively. Esophageal dysmotility, lower esophageal sphincter laxity, bacterial overgrowth, and wide mouth diverticuli were the most common findings. The disease is usually diffuse with multiple levels of involvement. Gastrointestinal involvement was not significantly correlated with gender, age at SSc diagnosis or disease type (limited or diffuse scleroderma). Upper GI symptoms develop early in the course of SSc and may not correlate with objective findings. Various investigations, treatment regimens, and less frequent disease manifestations are reviewed and discussed.

Fibromyalgia syndrome in men.

OBJECTIVE: Fibromyalgia syndrome (FMS) is uncommon in men and data on its characteristics and severity are limited. The current study was undertaken to determine whether the clinical characteristics and the spectrum of this disorder are similar in men and women. METHODS: Forty men with FMS were matched with 40 women by age and educational level. All subjects were asked about the presence and severity (assessed by visual analog scale) of FMS symptoms; a count of 18 tender points was conducted by thumb palpation, and tenderness thresholds were measured by dolorimetry. Psychological status was assessed by the anxiety and depression subscales of the revised Arthritis Impact Measurement Scales. Quality of life was evaluated by two scales, QOL-16 and SF-36, and physical function was measured by the Fibromyalgia Impact Questionnaire. RESULTS: Men with FMS reported more severe symptoms than women, decreased physical function, and lower quality of life. Women had lower tender thresholds than men; however their mean point counts were similar. CONCLUSION: Although FMS is uncommon in men, its health outcome in our study population was worse than in women. Further studies in larger samples and in diverse ethnocultural populations are needed to confirm this observation.

The prevalence of musculoskeletal pain and fibromyalgia in patients hospitalized on internal medicine wards.

OBJECTIVES: To estimate the prevalence of nonarticular pain complaints (chronic widespread pain, chronic localized pain, transient pain) and fibromyalgia in hospitalized patients and to study utilization patterns of health services associated with pain related problems. METHODS: Five hundred twenty-two patients hospitalized on internal medicine wards were enrolled. Data were collected with a questionnaire covering demographic background, information on pain and other symptoms, utilization of health services, and drug consumption. All subjects were classified into four pain groups: those with no pain, transient pain, chronic regional pain, and chronic widespread pain. Tenderness was assessed by thumb palpation, and patients were diagnosed as having fibromyalgia if they met the 1990 American College of Rheumatology criteria. RESULTS: Sixty-two percent of the patients reported pain; 36% reported chronic regional pain, 21% reported chronic widespread pain, and 5% reported transient pain. Fifteen percent of all patients had fibromyalgia, most of whom (91%) were women. The prevalence of chronic widespread pain and of fibromyalgia in women increased with age. Sleep problems, headache, and fatigue were highly prevalent, especially among those with chronic widespread pain. Patients with chronic widespread pain reported more visits to family physicians (6.2 visits per year) and more frequent use of drugs. They also were more frequently referred to rheumatologists, and they reported more hospitalizations. CONCLUSIONS: Pain syndromes and related symptoms are prevalent among hospitalized patients on the medicine wards. The internist taking care of these patients should be aware of the presence of these syndromes and realize that some of the reported symptoms are partly related to these (undiagnosed) pain syndromes rather than to the cause of hospitalization.

Frontiers of SLE: review of the 5th International Congress of Systemic Lupus Erythematosus, Cancun, Mexico, April 20-25, 1998.

OBJECTIVE: To review the recent advances in clinical and experimental research in systemic lupus erythematosus (SLE). METHODS: Review of the 5th International Congress of SLE that took place in Cancun, Mexico, on April 20-25, 1998. RESULTS: The main topics presented at the conference are summarized. These include new findings about the genetics of SLE due to fine mapping of the patients' genes and lupus mouse models, the nucleosome as a major autoantigen in SLE, serving as an immunogen for pathogenic T helper and B cells and contributing to the development of lupus nephritis, abnormalities of apoptosis as a cause of SLE, and apoptotic mechanisms as a cause of autoimmunization. Other topics included the pathophysiologic role of anti-endothelial cell antibodies in lupus with central nervous system involvement, vasculitis, the thrombotic diathesis associated with the antiphospholipid syndrome, induction of endothelial cell apoptosis and its regulation by the idiotypic network, the penetration of antinuclear antibodies to the cytoplasm and nucleus and the subsequent interaction with cellular organelles, and new aspects in the antiphospholipid syndrome, including animal models of the disease and the importance of antibodies to beta-2-glycoprotein-I and prothrombin. Advances in the clinical aspects of SLE included clinical manifestations, diagnosis, pregnancy and neonatal SLE, infections, hormones, and treatment. Additionally, four "Lectures of A Lifetime," entitled (1) What causes lupus? (2) From natural autoimmunity to autoimmune disease; (3) The idiotypic network and SLE; and (4) Late-stage morbidity and mortality in SLE-the role of accelerated atherosclerosis were presented. CONCLUSIONS: Recent advances provide new insights into the pathogenesis of SLE, as well as hope for novel therapeutic modalities and diagnostic measures. These offer the possibility of improving life quality and decreasing mortality from the disease and its complications.

Parasitic infection and autoimmunity.

The studies summarized in this paper indicate that parasitic infections can serve as a trigger factor of autoimmune reactivity by several mechanisms. The relationship between parasites and autoimmunity could be manifested by the presence of autoantibodies or T-cells with autoreactivity. In spite of the evidence that has accumulated, the specific association between infection and autoimmunity is still obscure. The reasons for tissue damage in parasitic diseases are controversial. Some believe it is the result of pathogenic autoantibodies or autoreactive T-cells. Others argue against the causative role of autoimmunity in the formation of tissue lesions. The parasite itself could be the cause of tissue destruction, thus releasing high amounts of self antigens which might stimulate the autoreactivity. There is now little doubt that some degree parasite/host cross-reactivity occurs, and definition of cross-reacting antigens and epitopes is now taking place. It seems likely that a combination of events could result in cross-reactivity including: parasites themselves have cross reactive molecules and altered self antigens by adsorbing of parasite material to surrounding host cells. The mechanisms involved in parasites autoimmunity are complex and numerous, requiring a rigorous experimental approach to rationalize each step and determine its clinical importance. The developed methods in immunochemistry, monoclonal antibodies and hybridoma technology, and recombinant DNA research not only facilitate this kind of approach but also allow optimism for a successful outcome.

The role of spa therapy in various rheumatic diseases.

Spa therapy seems to have a role in the treatment of a broad range of joint diseases. It cannot substitute for conventional therapy but can complement it. The improvement reported in some of the studies is of short duration, lasting for months. It should be considered for patients suffering from various types of inflammatory arthritides or noninflammatory arthritides who are symptomatic, despite accepted medical therapy and conservative physiotherapy, if they can afford the expense. The patients should be told that the effectiveness and success of this therapy cannot be predicted in advance. Because we have no way to date, of curing most rheumatic diseases, clinical trials of alternative therapeutic methods are justified. These methods may alleviate patient suffering and are almost totally devoid of serious adverse effects. No studies have been reported that evaluate their cost-effectiveness.

Living with a child with familial Mediterranean fever: does it affect the quality of life of the parents?

OBJECTIVE: The aim of the present study was to assess the quality of life (QOL) and the psychological status of parents of children with familial Mediterranean fever (FMF). METHODS: The QOL, anxiety and depression of the parents of 35 children with FMF were evaluated and compared to the parents of 23 healthy children. RESULTS: Mothers of FMF children had lower QOL scores than mothers of healthy children: 5.5 +/- 1.1 versus 6.0 +/- 0.6 (p = 0.048). They also expressed higher levels of anxiety and depression. Within each group, mothers were more anxious and depressed than fathers. Parents with several FMF children were not significantly different from parents with only one FMF child. CONCLUSION: The QOL and psychological well being of parents with FMF children were found to be slightly impaired, especially that of the mothers.

Features of SLE in various ethnic groups in Israel.

OBJECTIVE: To assess the association between the ethnic origin of patients with SLE living in Israel, and the clinical and laboratory features of SLE. METHODS: A retrospective review of medical records was carried out. Patients were classified into 3 groups based on their ethnic origin: a) Ashkenazi Jews, b) Sepharadic Jews and c) Arabs. RESULTS: The study included 74 consecutive SLE patients, 69 (93%) women and 5 (7%) men. Their mean age at diagnosis was 32 years and their mean disease duration was 6.4 years. There were 21 (28%) Ashkenazi Jews, 31 (42%) Sepharadic Jews and 22 (30%) Arabs. The demographics, the frequency of various clinical and laboratory variables of SLE, and the mean disease activity index score (SLEDA1) of the three groups were not statistically different. CONCLUSION: The ethnic origin of SLE patients living in Israel is not associated with the clinical and laboratory features of the disease.

Systemic sclerosis: another rheumatic disease associated with hepatitis C virus infection.

The first case of a patient with chronic infection with hepatitis C virus who developed systemic sclerosis, manifested by severe Raynaud's phenomenon, progressive skin thickening, painful fingertip ulcers, dysphagia and Sjogren's syndrome, is described. The role of interferon therapy is discussed.

Influenza virus vaccination of patients with SLE: effects on generation of autoantibodies.

The sera of 24 women with SLE who received influenza vaccine were tested by ELISA for anti-DNA, anticardiolipin, anti-Sm, anti-Sm/RNP, anti-Ro and anti-La. Blood samples were withdrawn at the time of vaccination and 6 and 12 weeks after vaccination. The mean age at enrolment into the study was 46.1 years. The mean disease duration was 9.1 years. SLEDAI scores were 6.6 at vaccination, 4.9 at 6 weeks and 5.1 at week 12. The vaccine was not associated with the generation of anti-DNA. At time of vaccination a single patient had anti-Sm, four patients had anti-Sm/RNP antibodies, none of the patients had anti-La antibody and six had anti-Ro antibodies. Six weeks after vaccination four, eight, nine and three patients had autoantibodies reacting with Sm, Sm/RNP, Ro and La, respectively. Twelve weeks after vaccination none of the patients had anti-Sm, three had anti-Sm/RNP, five had anti-Ro and two had anti-La antibodies. Following vaccination six and three patients developed IgG and IgM anticardiolipin antibodies, respectively. In summary, although the influenza virus vaccine is clinically safe for patients with SLE it may trigger the generation of autoantibodies. This effect is usually short term and has no clinical significance.

Anti-Sm-RNP activity in sera of patients with rheumatic and autoimmune diseases.

The sera of various rheumatic and autoimmune diseases were examined for the presence of anti-RNP/Sm activity. An enzyme-linked immunosorbent assay (ELISA) was employed. Anti-RNP Ab's were detected in 18%, 20%, 28%, 16% of the sera of SLE, myasthenia gravis (MG), rheumatoid arthritis (RA) and thyroid diseases respectively. The anti-RNP Ab's belonged to the IgG and IgM isotypes. Most of the IgG anti-Sm antibodies were detected in SLE sera, but they were found also in two sera of MG and in one sera of RA patients. IgM anti-Sm antibodies were not found in SLE sera, but they were detected in low titer in MG, RA and autoimmune thyroid diseases. The activity against RNP and/or Sm was further confirmed by employing immunoblotting assays. In none of the patients, except those with SLE, was any clinical manifestation of SLE noted. The mere presence of anti-Sm antibodies of the IgG isotypes is not sufficient for the development of SLE, however, its presence is highly specific for SLE.

The effect of balneotherapy at the Dead Sea on the quality of life of patients with fibromyalgia syndrome.

Fibromyalgia (FS) is an idiopathic chronic pain syndrome defined by widespread non-articular musculoskeletal pain and generalised tender points. As there is no effective treatment, patients with this condition have impaired quality of life (QoL). The aim of this study was to assess the possible effect of balneotherapy at the Dead Sea area on the QoL of patients with FS. Forty-eight subjects participated in the study; half of them received balneotherapy, and half did not. Their QoL (using SF-36), psychological well-being and FS-related symptoms were assessed prior to arrival at the spa hotel in the Dead Sea area, at the end of the 10-day stay, and 1 and 3 months later. A significant improvement was reported on most subscales of the SF-36 and on most symptoms. The improvement in physical aspects of QoL lasted usually 3 months, but on psychological measures the improvement was shorter. Subjects in the balneotherapy group reported higher and longer-lasting improvement than subjects in the control group. In conclusion, staying at the Dead Sea spa, in addition to balneotherapy, can transiently improve the QoL of patients with FS. Other studies with longer follow-up are needed to support our findings.

Balneotherapy at the Dead Sea area for knee osteoarthritis.

BACKGROUND: Balneotherapy at the Dead Sea area has been applied in various inflammatory rheumatic diseases such as rheumatoid arthritis and psoriatic arthritis. The efficacy of balneotherapy at the Dead Sea area for the treatment of degenerative rheumatic diseases has not yet been formally evaluated. OBJECTIVE: To evaluate the efficacy of balneotherapy at the Dead Sea area in patients suffering from osteoarthritis of the knees. METHODS: Forty patients were randomly allocated into four groups of 10 patients. Group I was treated by bathing in a sulphur pool, group 2 by bathing in the Dead Sea, group 3 by a combination of sulphur pool and bathing in the Dead Sea, and group 4 served as the control group receiving no balneotherapy. The duration of balneotherapy was 2 weeks. RESULTS: Significant improvement as measured by the Lequesne index of severity of osteoarthritis was observed in all three treatment groups, but not in the control group. This improvement lasted up to 3 months of follow-up in patients in all three treatment groups. CONCLUSION: Balneotherapy at the Dead Sea area has a beneficial effect on patients with osteoarthritis of the knees, an effect that lastas at least 3 months.

Balneotherapy at the Dead Sea area for patients with psoriatic arthritis and concomitant fibromyalgia.

BACKGROUND: Balneotherapy has been successfully used to treat various rheumatic diseases, but has only recently been evaluated for the treatment of fibromyalgia. Since no effective treatment exists for this common rheumatic disease, complementary methods of treatment have been attempted. OBJECTIVES: To assess the effectiveness of balneotherapy at the Dead Sea area in the treatment of patients suffering from both fibromyalgia and psoriatic arthritis. METHODS: Twenty-eight patients with psoriatic arthritis and fibromyalgia were treated with various modalities of balneotherapy at the Dead Sea area. Clinical indices assessed were duration of morning stiffness, number of active joints, a point count of 18 fibrositic tender points, and determination of the threshold of tenderness in nine fibrositic and in four control points using a dolorimeter. RESULTS: The number of active joints was reduced from 18.4 +/- 10.9 to 9 +/- 8.2 (P < 0.001). The number of tender points was reduced from 12.6 +/- 2 to 7.1 +/- 5 in men (P < 0.003) and from 13.1 +/- 2 to 7.5 +/- 3.7 in women (P < 0.001). A significant improvement was found in dolorimetric threshold readings after the treatment period in women (P < 0.001). No correlation was observed between the reduction in the number of active joints and the reduction in the number of tender points in the same patients (r = 0.2). CONCLUSIONS: Balneotherapy at the Dead Sea area appears to produce a statistically significant substantial improvement in the number of active joints and tender points in both male and female patients with fibromyalgia and psoriatic arthritis. Further research is needed to elucidate the distinction between the benefits of staying at the Dead Sea area without balneotherapy and the effects of balneotherapy in the study population.

[Recurrent avascular bone necrosis in systemic lupus].

Ischemic necrosis of the bones in systemic lupus erythematosus (SLE) usually appears when treatment with corticosteroids is initiated. The most frequent site is the hip, while the knee and shoulder are less frequently involved. A 21-year-old man was admitted because of bilateral shoulder pain 3 years after diagnosis of SLE. The skin, joints, brain, small intestine and kidneys were also involved and corticosteroid therapy was started. 1.5 years before his last admission, severe knee pain developed with limitation of range of movement but without effusion or soft tissue swelling. Bone scan confirmed the diagnosis of aseptic necrosis of the femur and tibia of both knees. He also developed bilateral shoulder pain accompanied by limitation of the range of internal and external rotation. X-ray of the shoulders demonstrated bilateral ischemic necrosis. Since synovitis is relatively rare in SLE treated with corticosteroids, aseptic necrosis of the bone should always be suspected when arthralgia develops in this condition.